Research on the "genetics of the rotaviruses" will focus on three main areas: (1) Genetic analysis -- We will continue our genetic anaysis of the rotaviruses including isolation temperature-sensitive (ts) mutants and grouping them by recombination analysis. THe physiologic properties of the mutant groups will be examined, with emphasis on synthesis and regulation of synthesis of single- and double-stranded RNA, proteins, morphogenesis and virion transcriptase. Recombinants segregating the genome segments of two parents will be isolated and segregation patterns of genome segments in the recombinants will be used to map ts lesions to specific genome segments and establish a map of genes encoding identical function in the two viruses. The proteins synthesized by the recombinants will be examined to establish the coding relationships between specific protein species and specific genome segments. The goal of this analysis is to isolate ts mutations that identify each of the viral genes. (2) Analysis of pathogenesis -- We will use recombinants, in which the parental origin of each gene is defined, to identify the viral gene encoding the neutralization antigen and hemagglutinin. The behavior of the recombinants following oral inoculation of mice will be used to determine the viral gene(s) that control virulence of infection, replication in the gastrointestinal (GI) tract, and tropisms of the virus for tissues outside the GI tract. The role of recombination in GI tract infection will be examined. (3) Analysis of viral variation -- Revertants of ts mutants will be examined to determine the mechanism of reversion and the possibility of extragenic suppression of ts phenotype. Persistent infections of permissive cells will be examined, with emphasis on viral variation during persistence and the possible role of this variation in viral epidemiology. These studies will provide basic information on the interaction of enteric viruses with the host, may reveal unique pathogenic pathways characteristic of rotavirus infection, and will provide information useful for vaccine development.